How do we measure age? New study comes up with new answers

Using saliva or cheek swabs can overestimate biological age by up to 30 years.

 How do we measure age? New study comes up with new answers. Illustration. (photo credit: Alejandro_Munoz. Via Shutterstock)
How do we measure age? New study comes up with new answers. Illustration.
(photo credit: Alejandro_Munoz. Via Shutterstock)

Our bodies don't always age in line with the number of candles on our birthday cakes. According to researchers at Penn State University, a person's biological age—which reflects how well their body is functioning—can differ from their chronological age, which is simply the number of years since birth. This discrepancy can be influenced by various stressors experienced over a lifetime, potentially making our bodies "older" or "younger" than we might expect.

Scientists have developed methods to estimate biological age, but a recent study led by Abner Apsley, a doctoral candidate at Penn State's Molecular, Cellular, and Integrative Biosciences Graduate Program, highlights that the type of tissue used for measurement is crucial. Apsley and his adviser, Associate Professor Idan Shalev, published their findings in the journal Aging Cell.

Biological age is gaining attention as it can provide a more precise understanding of an individual's risk for age-related diseases, including cancers and dementia. Researchers have created several epigenetic clocks—tools that compare a person's biological age to their chronological age. These clocks are constructed by collecting tissue samples from a large number of people and examining differences in epigenetic markers across the lifespan. Using machine learning, scientists identify which epigenetic markers predict chronological age to determine if a person's epigenome matches their chronological age.

Multiple companies have begun offering services that estimate people's biological age by analyzing epigenetic information from customers' saliva samples, which are mailed in after spitting into a test tube. However, most epigenetic clocks are created using blood, not saliva. In clinical settings, scientifically validated uses of epigenetic clocks are not yet common, and the accuracy of these commercial tests may be questionable due to the tissue type used.

The researchers wanted to compare the performance of different tissue-sample types in estimating biological age. They evaluated five types of tissue samples and compared them with seven epigenetic clocks. The study included 284 distinct tissue samples from 83 individuals between the ages of nine and 70 years old. In six of the seven clocks tested, the team found that oral tissue resulted in substantially less accurate estimates of biological age than blood-based samples.

"We tested three types of blood samples and two types of oral tissues—saliva and cheek swabs," said lead author Abner Apsley. "For almost every epigenetic clock, the oral tissue led to significantly higher estimates of the subject's biological age. In some cases, the estimates were 30 years higher; that is extremely inaccurate. It is very clear that the tissue used to measure someone's biological age must match the tissue used when the clock was created. Otherwise, estimates of biological age will not be valid."

Results from the study demonstrated that blood-tissue types led to similar biological age estimates across the different epigenetic clocks. In contrast, oral tissue performed very differently and was generally not as accurate, often estimating older biological ages. The one exception was the only epigenetic clock in the study created using both blood and cheek swabs. For that clock, the age estimates across different tissues were much more accurate.

"Most of the popular clocks were created using blood samples," Apsley noted. "So, these results represent an important lesson for this burgeoning field. If companies or physicians want to use saliva or cheek swabs to measure biological age, then researchers need to develop epigenetic clocks using those tissues. Currently, blood is needed to accurately estimate biological age in most circumstances."

Understanding a person's biological age could have significant implications for healthcare. "Aging is the main driver for a host of common diseases including dementia, heart disease, and cancer," said Idan Shalev. "Measurement of biological age is not a diagnosis of a health problem, but it can be used to identify a person's risk for age-related conditions."

While tests of biological age are not commonly measured in medical settings yet, they could someday be used to identify patients who may need medication to delay the onset of an age-related disease due to their advanced biological age. Patients with delayed biological age might be better candidates for surgery than others of the same chronological age.


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"Researchers are still discovering how to apply biological age," Shalev added. "Our research focuses on medical applications, but epigenetic clocks have also been used with blood samples from crime scenes to help forensic scientists identify the approximate age of criminal suspects. Who knows where this field will lead us next?"

The article was written with the assistance of a news analysis system.